A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

Fogleman et al., The Journal of the American Board of Family Medicine, doi:10.3122/jabfm.2022.04.210529, NCT04530539

Jul 2022

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Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).

This is the 13th of 16 COVID-19 RCTs for vitamin C, which collectively show efficacy with p=0.00000018.

This is the 50th of 63 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000026.

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This study includes vitamin C and melatonin.

relative recovery, 4.4% better, RR 0.96, p = 0.83, treatment mean 17.59 (±13.1) n=32, control mean 16.82 (±15.7) n=34, mid-recovery, relative symptom improvement, day 9.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Fogleman et al., 27 Jul 2022, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, mean age 52.0, 7 authors, study period 5 October, 2020 - 21 June, 2021, average treatment delay 6.0 days, trial NCT04530539 (history).

Contact: corey.fogleman@pennmedicine.upenn.edu.

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A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

MD, FAAFP Corey Fogleman, MD, MSc Donna Cohen, MD Alison Mercier, MD Daniel Farrell, MD Jennifer Rutz, MS Kellie Bresz, MPH Tawnya Vernon

The Journal of the American Board of Family Medicine, doi:10.3122/jabfm.2022.04.210529

This study aimed to help determine the effect of dietary supplements on symptom course and quality of life in patients with mild-to-moderate COVID-19 infection. Design: We modified the Wisconsin Upper Respiratory Symptom Survey (WURSS) to conduct a 3 arm, parallel, randomized, double-blind, placebo-controlled trial, enrolling patients with mild-to-moderate symptoms of COVID-19 infection. Patients took placebo (n = 34), vitamin C 1000 mg (n = 32), or melatonin 10 mg (n = 32) orally for 14 days. Outcomes: Ninety Eight (98 out of 104 recruited; mean age = 52 years) patients completed the study. Outcomes were calculated as differences from baseline scores on each of 2 WURSS-derived surveys and analyzed using a spline regression analysis. Regarding symptom progression, those patients taking placebo and vitamin C progressed at the same rate. When compared with those taking placebo (coefficient = -1.09 (95% confidence interval [CI] = -1.39 to -0.8) the group taking melatonin had a faster resolution of symptoms (coefficient = -0.63 [95% CI -1.02 to -0.21] P = .003). By day 14 all 3 groups had reached plateau. Quality-of-life impact analysis demonstrated that the group taking vitamin C improved at the same rate as the group taking placebo (coefficient = -0.71 (95% CI = -1.11 to -0.3)). The group taking melatonin (coefficient = -1.16 (95% CI = -1.75 to -0.57) P < .005) had a faster improvement in quality-oflife. By day 14 all 3 groups had reached plateau. Conclusion: Vitamin C 1000 mg once daily has no effect on disease progression. Melatonin 10 mg daily may have a statistically significant effect but it is unclear if this represents a clinically significant benefit to those with mild-to-moderate symptoms of COVID-19 infection. Further study is warranted. ( J Am Board Fam Med 2022;35:695-707.

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